JP2021536660A - Plasma polymerization equipment - Google Patents

Abstract

Reaction zone, at least one gas inlet for supplying at least one monomer in the form of gas to the reaction zone, spaced apart, creating an electric field in the reaction zone, plasma polymer nanoparticles material from at least one monomer A first electrode and a second electrode configured to form the A plasma polymerization apparatus is disclosed, which comprises a plurality of collectors arranged in a row thereof and a cooling device arranged adjacent to a second electrode and configured to cool the plurality of collectors. Also disclosed is a plasma polymerization apparatus comprising a confinement grid extending between a first electrode and a second electrode of the apparatus. [Selection diagram] Fig. 1

Description

Cross-reference to related applications This application claims the priority benefit of Australian Provisional Patent Application No. 2018903344 filed on September 7, 2018, the entire contents of which are incorporated herein by reference. ..

The present application relates to nanoparticles materials such as nanoparticles and aggregates thereof, including plasma-derived nanoparticles, which can be used to form conjugates. The present application also relates to methods and devices for collecting nanoparticle materials.

Multifunctional nanocarriers capable of delivering multiple molecular cargos within the same structure are expected to significantly improve both therapeutic and diagnostic outcomes for many diseases. However, current nanoparticle-based therapies and diagnostics still utilize materials that are essentially bioactive and probably do not allow direct and simple conjugation with pharmaceuticals. Functionalization of nanoparticles (eg, gold, iron oxide, polymers, quantum dots, etc.) is usually complex and generally time to achieve robust conjugation between the nanocarrier surface and the associated cargo. Depends on a multi-step protocol that requires.

Despite the recent rapid growth in nanomedical research, there is a need for new nanofabrication strategies that can provide new products with improved performance, functionality, and patient safety. For example, pharmaceutical nanocarriers currently commercially approved in the field of drug delivery in humans are based on the concept of passive targeting. In passive targeting, carriers rely on their small size to penetrate the abnormal leaky vasculature of pathological sites such as tumors and inflamed areas. While these nanoparticle-drug systems can sometimes increase the effectiveness of treatment, there remain drawbacks in biodistribution and site accumulation of the drug when compared to other alternative therapies. The prospect of reducing side effects of the drug and increasing dose tolerance has not been realized. In this regard, considerable efforts have been made to develop potential nanocarrier platforms that provide selective delivery of dose-tolerant active targeting.

To achieve specific and targeted delivery in a wide range of therapeutic applications, nanoparticles can be functionalized with a variety of target ligands that recognize and bind to specific surface signatures expressed in target cells. can. The complexity of various signaling pathways in multifactorial diseases such as cancer has paved the way for the development of multidrug inhibitor-based therapies that can avoid treatment resistance. Importantly, combining different drugs within or on the same nanocarrier increases the effectiveness of the multidrug approach. In addition, it is desirable to achieve good control and monitoring of the nanoparticle system during medical imaging treatment, which means that it is also advantageous for the nanoparticles to incorporate the appropriate contrast agent. Therefore, there is a strong need to develop multifunctional nanoparticles that can achieve coordinated mixing of different functions while integrating both targeted therapy, diagnosis, and imaging within the same nanostructure. However, the ability to bind multiple molecular cargoes on the same nanocarrier is particularly elusive in this area.

In addition, there is considerable room for therapeutic delivery of nucleic acids, including DNA, mRNA, and siRNA to regulate the expression of aberrant proteins in the disease. This approach has shown considerable promise in vitro, but has not been fully realized clinically, that is, for in vivo treatment. Among some drawbacks, especially when administered systemically, these molecules are highly unstable in the blood and are filtered by the kidneys and liver, and their highly charged state is a hand that crosses the cell membrane. Prevents fast transportation. Furthermore, upon passing through the cell membrane, mRNA and siRNA need to escape endosomes to reach the cytoplasm and gain activity, whereas DNA needs to enter the nucleus. Nanoparticle platforms containing liposome nanoparticles have been used to facilitate delivery with moderate success, but nevertheless this is hampered by toxicity and long-term intracellular persistence issues. There is. Nanoparticle platforms capable of transporting this type of cargo to the cytoplasm or nucleus in a preferentially targeted manner across the cell membrane show significant progress in this field.

Nanoparticles with surfaces that can provide robust chemical conjugation sites are a major advance in the field. On current platforms, one of the limitations in combining multiple functions of nanoparticles in a single structure is the actual surface chemistry of nanoparticles. Bonding through chemical bonds is preferred over weaker non-covalent strategies for better control over various functions of nanocarriers. To overcome this challenge, a common strategy adopted by many commercial platforms is to graft polymers such as poly (ethylene glycol) (PEG) onto nanoparticles. However, these coating and functionalization strategies include complex, multi-step, time-consuming protocols that often contain solvents that pose safety or disposal issues. Moreover, optimization, reproducibility, and control of PEG surface concentration and thickness are usually difficult to achieve with these conjugation processes. Usually, the end groups of the coating ligand also limit the range of biomolecules that can be immobilized. Other conjugation strategies include pre-conjugation of molecules and nanoparticle materials in the self-assembling process. However, these latter approaches also rely on the use of organic solvents and multiple purification steps that compromise the original conformation and function of the molecular cargo. The use of multiple synthesis steps can also reduce the final yield of functionalized nanoparticles.

Therefore, an improved process is needed to produce activated nanoparticles for conjugation with the therapeutic and / or imaging moieties. Ideally, activated nanoparticles should be functionalized with multiple functional molecules using a simple approach, such as direct incubation with a solution containing biomolecules.

Plasma polymerization (PP) has been established as the preferred surface deposition platform for technical and biomedical applications. The plasma reaction environment fragmentes the monomers, ionizes them into building blocks, polymerizes and diffuses towards the plasma boundaries, causing surface polymerization. Ultimately, the diffusion of these reactive blocks out of the plasma can result in the deposition of thin films with modulated properties.

In some PP reactions, thin film deposition (surface polymerization) occurs at the same time as plasma bulk polymerization to form charged plasma dust particles, ie plasma dust or dust plasma. For example, ionization of acetylene in plasma causes the continuous formation of carbonaceous nanoparticles that aggregate to form nano-sized to micron-sized charged particles in the plasma volume, resulting in the formation of plasmapolymer nanoparticles (PPN).

It has been proposed that PPNs with adjustable physical and chemical properties may function as a new class of nanoparticles for use in a wide range of nanomedical applications. Plasma polymerization of nanoparticles in dust plasma provides a viable synthetic platform. However, when nanomedical applications are applied, such as in clinical applications, nanoparticles should be made of biocompatible materials that are easy to function.

Recently, carbon-based PPN (nanoP ³ ) has been recognized as a versatile nanocarrier capable of delivering biofunctional cargo without inducing cytotoxicity (see Santos et al. 2018, ACS Applied Materials & Surfaces). ing. Nano P ³ is obtained at the surface of the nano-P ³ is a reactive, are formed on the acetylenic plasma through the assembly of reactive carbon cluster spherical nanoparticles. Radicals and functional surface groups easily immobilize a wide range of functional biomolecules by simple one-step incubation in aqueous solution.

PPN formed in the bulk of a plasma reactor has long been considered an undesired by-product in technical applications. Growth of PPN followed by surface deposition represents a source of contamination in the synthesis of microcomponents. Therefore, most of the research in the field of dust plasma aims to combine modeling and experimental tools to understand the formation of dust particles in reactive plasmas and to control the dynamics of the particles to eliminate or remove them from the reactor. It is supposed to be.

In this regard, a general strategy for removing PPN involves the application of external forces to manipulate the dynamics of the particles, eg, using a magnetic field, to allow the collection of the particles. However, such collection methods are often characterized by low nanoparticle yields, polydisperse PPN size, or irreversible aggregation. In addition, they often require modification of existing plasma chambers with specialized equipment (eg, power supplies, vacuum feedthroughs) that increases cost and design complexity. The development of high-yield, efficient collection strategies that minimize nanoparticle agglomeration has not yet been reported.

Therefore, an improved process is needed to collect the PPN formed by the plasma polymerization of nanoparticles in the dust plasma.

Any description of any document, act, material, device, article, etc. contained herein, in any or all of these matters, forms part of the basis of the prior art, or each claim of the present application. It should not be construed as an endorsement of the common wisdom in the art of this disclosure that existed prior to the priority date of the paragraph.

According to one aspect of the present disclosure, a plasma polymerization apparatus is provided, which is a device.
Reaction zone,
At least one gas inlet for supplying at least one monomer in the form of a gas to the reaction zone,
First and second electrodes, spaced apart and configured to generate an electric field in the reaction zone to form a plasmapolymer nanoparticle material from at least one monomer.
Multiple collectors configured to collect the plasmapolymer nanoparticle material formed in the reaction zone, adjacent to the second electrode and adjacent to the second electrode. Includes a cooling device that is arranged and configured to cool multiple collectors.

According to another aspect of the present disclosure, a plasma polymerization apparatus is provided, which is a device.
Reaction zone,
At least one gas inlet for supplying at least one monomer in the form of a gas to the reaction zone,
First and second electrodes, spaced apart and configured to generate an electric field in the reaction zone to form a plasmapolymer nanoparticle material from at least one monomer.
A plurality of collectors configured to collect the plasma polymer nanoparticle material formed in the reaction zone, the plurality of collectors arranged adjacent to the second electrode, and the first electrode and the second electrode. Includes a confinement grid that extends between the electrodes.

In another aspect of the present disclosure, a method of collecting plasma polymer nanoparticle material is provided, wherein the method is:
Supplying the reaction zone with at least one monomer in the form of a gas,
Creating an electric field in the reaction zone between the first electrode and the second electrode spaced apart from the first electrode to form the plasmapolymer nanoparticle material from at least one monomer.
In multiple collectors adjacent to the second electrode, collect plasma polymer nanoparticle material formed in the reaction zone, and use multiple collectors with a cooling device located adjacent to the second electrode. Includes cooling.

In yet another aspect of the present disclosure, a method of collecting plasma polymer nanoparticle material is provided, which method is:
Supplying the reaction zone with at least one monomer in the form of a gas,
Creating an electric field in the reaction zone between the first electrode and the second electrode spaced apart from the first electrode to form the plasmapolymer nanoparticle material from at least one monomer.
Plasma polymer nanoparticles material formed in reaction zones at multiple collectors adjacent to the second electrode and confining the plasma using a confinement grid extending between the first and second electrodes. Including collecting.

Here, embodiments of the present disclosure will be described only by way of reference with reference to the drawings.

FIG. 1a shows a cross-sectional view of a plasma polymerization (PP) apparatus according to an embodiment of the present disclosure. FIG. 1b shows a cross-sectional view of a modified portion of the plasma polymerization (PP) apparatus of FIG. 1a.

A cross-sectional view of a plasma polymerization (PP) apparatus according to another embodiment of the present disclosure is shown. The perspective view of the apparatus of FIG. 2a is shown.

FIG. 6 shows a schematic diagram of the plasma process input parameters and the electronic components of the controller for controlling the cooling applied by the cooling device of the PP device of FIGS. 1a, 1b and 2.

FIG. 4a shows a schematic representation of the collection of PPN in a dust plasma using a three-dimensional collector (removable well plate containing a plurality of wells) using the PP apparatus according to the embodiments of the present disclosure. For comparison, a conventional two-dimensional collector (ie, no wells) is shown in FIG. 4b.

A schematic comparison of the dynamics of PPN in the presence of a flat 2D collector (left) and a well-type 3D collector (right) is shown.

6a and 6b show a schematic comparison of PPN aggregation using multiple collectors according to embodiments of the present disclosure with different aspect ratios, showing that particle aggregation is inhibited in shorter wells. ..

Measured with a removable plate (well collector) when thermally coupled to both a single Pelce element and a cascade-mounted double Pelce element, and to a heat exchanger heat-coupled to the Pelche element. The plot of the temperature profile is shown. In addition, a comparison of the temperature stability of single and double Pelche element configurations is shown when a fan is used to dissipate the heat stored by the heat exchanger.

Production of nanoparticle material, the entire contents of which are described in detail in PCT Publication No. WO2018 / 112543, incorporated herein by reference, "Nano ^{P 3 (nanoP 3)"} or "nano ^{P 3} (NanoP ³⁾ "as described herein as" nano P ³ material (nanoP ^{3 material)} ", or" nano-P ³ material (NanoP ^{3 material).} "

These nano-P ³ materials can act as easily class of versatile and multifunctional nanocarriers can be functionalized. Nano P ³ material, the reaction via and / or nano-P ³ material or portion formed on a surface of the conjugates with embedded radicals in the nano-P ³ material to diffuse into the surface of the nano-P ³ material / Can bind to a wide range of biomolecules and drugs by reacting with functional groups.

The processes disclosed herein, such as plasma-based processes, are advantageous and adjustable physical, chemical, and morphological processes that can integrate multiple functions for a variety of nanomedical applications. It can be used to more effectively produce and collect nanoparticle materials with properties.

Definitions Throughout the specification, variants such as the word "comprise", or "comprises" or "comprising" are described elements, integers or steps, or elements, integers. Alternatively, it will be understood that it means the inclusion of a group of steps, but not the exclusion of any other element, integer or step, or group of elements, integers or steps.

Throughout the specification, the term "becoming essentially" may include elements that do not substantially affect the properties, but exclude elements that substantially affect the properties of the claimed composition. Intended to do.

With respect to the definitions presented herein, unless otherwise specified or implied by context, the defined terms and phrases include the meanings presented. Unless otherwise stated or apparent from the context, the following terms and phrases do not preclude the meaning gained by one of ordinary skill in the art concerned. The definition is presented to aid in the description of a particular embodiment and is not intended to limit the claimed invention, as the scope of the invention is limited only by the claims. Further, unless otherwise required by context, singular terms shall include the plural and plural terms shall include the singular.

Throughout the specification, various aspects and components of the invention can be presented in the form of a range. The form of scope is included for convenience and should not be construed as an inflexible limitation on the scope of the invention. Therefore, the description of the range should be regarded as specifically disclosing all possible sub-ranges and individual numbers within that range, unless otherwise stated. For example, descriptions in the range 1-5 are 1-3, 1-4,1-5,2-4,2-unless an integer is required or implicitly specified by the context. Specific disclosure of secondary ranges such as 5, 3-5, as well as individual and partial numerical values within the stated ranges such as 1, 2, 3, 4, 5, 5.5, 6. Should be considered. This applies regardless of the width of the disclosed range. If specific values are required, they are shown herein.

"about"
As used herein, the term "about" includes a 10% margin of error at any value (s) associated with the term.

"hydrocarbon"
The hydrocarbon monomers disclosed herein are understood to be monomers consisting only of hydrogen and carbon atoms. Examples of hydrocarbons include alkenes, alkynes, cycloalkenes, aromatic compounds, or mixtures thereof.

"Aggregate"
As used herein, unless otherwise stated or apparent from the context in which it is used, the term "aggregate" comprises multiple nanoparticle polymers and has a size in the range of 5 nm to 100 μm. For example, it is meant to mean particles having a size in the range of about 5 nm to about 500 nm.

"Conjugate"
As used herein, the term "conjugate" refers to a molecule formed by attaching one or more compounds to a nanoparticle polymer or an aggregate containing the nanoparticle polymer. "One or more compounds" can be the second species as defined herein. Adhesion may be via covalent bonds or electrostatic interactions.

"Inert gas"
The term "inert gas" can be activated under a given set of conditions, such as those commonly used to prepare nanoparticle polymers or aggregates thereof, as described herein. As such, it refers to a gas that can undergo a chemical reaction with one or more monomers, but it is not incorporated into a nanoparticle polymer or an aggregate thereof. Examples of the inert gas include, for example, helium, neon, and argon.

"monomer"
Unless otherwise stated, the term "monomer" is understood to mean a monomeric compound capable of reacting to form a polymer capable of being produced by a plasma fragmentation and reaction process with one or more reactive functional groups. To.

"Nano P ³ "
Unless clear from the context that other not specified, or used, the term "nano P ^3" refers to a nanoparticle material having a size less than 100 microns, for example, nano-P ³ is approximately 5~500nm Can have a size of. Unless expressly or implied by the context, ^{the term "nanoP 3} " is defined herein as "nanoparticle polymer" and "condensation" unless otherwise specified or apparent from the context in which it is used. Includes both "aggregates". The term "nano P ³ " can be used interchangeably with "nanoparticle material". In a preferred embodiment, the nanoparticle material comprises a plasma polymer. Plasma polymers can be formed by condensation of fragments in plasma, the material covalently bonding one or more compounds, eg, one or more "second species" containing organic or organometallic species. be able to.

"Nanoparticle polymer"
As used herein, the term "nanoparticle polymer" refers to a polymer formed of the monomers as defined herein, a nanoparticle polymer having a particle size in the range of about 1 nm to about 50 nm. In a preferred embodiment, the nanoparticle polymer is formed by condensation of fragments in plasma and the material can be covalently bonded to one or more compounds, including organic or organometallic seeds.

"polymer"
The term "polymer" refers to a compound or mixture of compounds made up of repeating structural units that can be non-uniform and / or can be arranged in a chaotic structure, created through the process of polymerization. Suitable polymers useful in the present invention are described throughout. In one embodiment, the polymer is a plasma polymer in which the repeating units are assembled into a relatively chaotic structure.

"plasma"
The term "plasma" generally refers to a (partially) ionized gas containing a mixture of ions, electrons, neutral species, and radiation. The plasma referred to herein comprises at least one monomer.

"Plasma polymer"
As used herein, a "plasma polymer" is a plasma-derived polymer containing one or more monomers. The plasma may also contain one or more reactive non-polymerizable (non-monomeric) gases and / or one or more inert gases.

"Reactive gas"
As used herein, the term "reactive gas" is generally activated under a given set of conditions, such as those used to prepare nanoparticle polymers or aggregates thereof, herein. Refers to a gas that undergoes a chemical reaction with one or more of the monomers described in 1.

Materials of the nano-P ³ described monomers herein may be at least partially derived from one or more monomers (derive) it. In one embodiment, one or more monomers are used in the form of gas to form a nano-P ³ material.

Examples of suitable monomers are described in PCT Publication No. WO2018 / 112543, page 18, lines 26-21, which are incorporated herein by reference.

As shown non-polymerizable reactive gas, nano P ³ materials described herein can be derived from one or more monomers and one or more non-polymerizable reactive gas. In one embodiment, the reactive gas of one or more non-polymerizable (not monomers) is activated, and reacted with one or more monomers to form a nano-P ^3. Fragments of the non-polymerizable reactive gas can be incorporated into the nanoparticle polymer or its aggregates.

An example of a suitable non-polymerizable reactive gas can be a Group 15, 16 or 17 gas in the Periodic Table. For example, the non-polymerizable reactive gas can be nitrogen (N ₂ ) gas or oxygen (O ₂ ) gas. Nitrogen as an example, obtained is particularly suitable for ensuring the hydrophobicity of reduction of nano-P ³ material occurs, which may optionally contain allows better dispersion of the nano-P ³ material in an aqueous solution Can be. For example, the nitrogen is present can lead to the presence of nano-amine particles polymers or nano-P ³ materials, imine or nitrile group, or mixtures thereof.

Nano P ³
Nano P ³ material may be a homopolymer or a copolymer. In one embodiment, the nano-P ³ material is a homopolymer. In another embodiment, the nano-P ³ material is a copolymer.

In one embodiment, the nano-P ³ is derived from plasma comprising one or more monomers described herein, which are initially present in the form of a gas. The one or more inert gases, such as helium, neon or argon, may optionally be present with the one or more monomers in combination with, for example, one or more non-polymerizable reactive gases.

Examples of a method of deriving an appropriate nano ^{P 3} materials and suitable nano ^{P 3} material, by reference to the line 12 of the second row to 28 pages of 21 pages of PCT Publication No. WO2018 / 112543, incorporated herein Has been described.

The aggregates aggregates can be formed during the production of nano-P ³ material, the polymer of the nanoparticles described herein.

In one embodiment, the aggregate has a size in the range of about 5 nm to about 100 μm, eg, about 5 nm to about 500 nm.

Nanoparticles polymers according to the conjugate herein, aggregates or nano P ³ material, in order to form a conjugate, one or more compounds, for example, defined organic compounds, organometallic compounds, or in the specification Can be bound to a second species that is made.

Details of the appropriate conjugates and methods for deriving the appropriate conjugates are described in PCT Publication No. WO 2018/112543, page 28, lines 18-40, which is incorporated herein by reference. ing.

Pharmaceutical Compositions Pharmaceutical compositions may include nanoparticle polymers, aggregates, or conjugates as defined herein, as well as pharmaceutically acceptable carriers, excipients, or binders. For details of the appropriate pharmaceutical composition and the method for deriving the appropriate pharmaceutical composition, see pages 7 to 26 of page 40 of PCT Publication No. WO 2018/11543 incorporated herein by reference. Has been described.

Therapeutic Methods Methods of treating an object suffering from, prone to, or exhibiting one or more symptoms of a disease, disorder, or condition are nanoparticle polymers, aggregates or conjugates thereof, as defined herein, or herein. It may include the step of administering to a subject a pharmaceutical composition as defined in the book. The nanoparticle polymers, aggregates or conjugates described herein can also be used in diagnostic tests.

Details of appropriate methods of treatment and diagnostic trials are described in PCT Publication No. WO 2018/112543, page 45, lines 1-48, which are incorporated herein by reference.

Substrate Nanoparticle polymers, aggregates, or conjugates as defined herein can be included in the substrate.

Details of suitable substrates are described in PCT Publication No. WO 2018/112543, page 48, lines 11-49, which are incorporated herein by reference.

Plasma polymerization according to embodiments of the product present disclosure nano ^{P 3} particles (PP) device 100 is shown in Figure 1a. The PP device 100 can be arranged inside the vacuum chamber 101. The PP apparatus 100 supplies at least one monomer in the form of a gas and, optionally, one or more additional gases, such as one or more non-polymerizable reactive gases, to the reaction zone 103 of the apparatus. Includes at least one gas inlet 102 of. The apparatus 100 also has a plurality of collectors arranged adjacent to the first electrode 104, the second electrode 105 separated from the first electrode 104 on the opposite side of the reaction zone 103, and the second electrode 105. The 106 and the cooling device 107 arranged adjacent to the second electrode 105 are included. The plurality of collectors 106 can be placed adjacent to the second electrode 105 by contacting the second electrode 105 and positioning it in close proximity, or at least partially inwardly. The cooling device 107 can be placed adjacent to the second electrode 105 by being in contact with the second electrode 105 and positioned in close proximity or even partially inward.

The PP device 100 can be used to collect plasma polymer nanoparticles materials formed in reactive plasmas, including nanoparticles and aggregates thereof. For example, as discussed in more detail below, the nanoparticle polymer and its aggregates can be formed using the PP apparatus 100 to supply at least one monomer in the form of a gas to the reaction zone 103. , Powering the first electrode 104 to generate plasma in the reaction zone to form plasmapolymer nanoparticles from at least one monomer, and using multiple collectors 106 to form in the reaction zone 103. It can be formed by a method including collecting the nanoparticles.

As shown, at least one monomer is provided in reaction zone 103 in the form of a gas. In this regard, at least one gas containing the monomer can be supplied to the reaction zone 103. At least one gas supplied may include at least one organic (ie, carbon-containing, non-carbon dioxide) gas. Further, the supplied at least one gas may include at least one non-polymerizable reactive gas and / or at least one inert gas. The at least one gas supplied to the vacuum chamber can have an absolute pressure in the range of about 1 to about 1500 Pa, for example about 6 Pa to about 67 Pa.

The non-polymerizable reactive gas may not be a monomer. The non-polymerizable reactive gas can be nitrogen (N ₂ ) gas. The non-polymerizable reactive gas can be an oxygen (O ₂ ) gas. The non-polymerizable reactive gas can be air. The non-polymerizable reactive gas can be a gas that is reactive with the nanoparticle material. In some embodiments, more than one non-polymerizable reactive gas can be supplied. The two or more non-polymerizable reactive gases can be a mixture of gases, for example a mixture of gases of argon, nitrogen and acetylene (carbon precursor). The gas components of the two or more non-polymerizable reactive gases can be individually supplied to the reaction zone 103. The gas components of the two or more non-polymerizable reactive gases can be supplied to the reaction zone 103 as a pre-prepared mixture.

Feeding a non-polymerizable reactive gas to a mixture of gases that can be fed to the reaction zone 103 cannot be dispersed in an aqueous solution and is due to the attachment of one or more compounds to the nanoparticle polymer or the aggregate containing the nanoparticle polymer. It can help reduce the formation of hydrophobic nanoparticle polymers and their aggregates that are unable to form conjugates.

The organic gas may contain hydrocarbons. The organic gas may contain carbon-carbon double bonds and / or carbon-carbon triple bonds. The organic gas can be an alkene or an alkyne. The organic gas can be a mixture of such gases. The organic gas may be polymerizable under the conditions of the process according to the present disclosure. In some embodiments, more than one organic gas can be supplied.

In one embodiment, the at least one gas comprises a mixture of two or more gases. One gas in the mixture can be an inert gas that is not incorporated into the nanoparticle polymer or its aggregates. At least one gas can be prepared from the individual constituent gases prior to being introduced into the vacuum chamber 101, or the gases of the individual components of the gas can be introduced into the vacuum chamber 101 separately. can. In the latter case, the proportion of constituent gases of at least one gas can be controlled by controlling different flow rates of different components. If at least one of the gases contains three or more distinct components, then at least one of the gases introduced into the reaction zone 103 can itself be a mixture, or else each separate constituent gas is separate. Can be introduced in. The constituent gas may include an organic gas and may also include one or more carrier gases, one or more non-polymerizable gases, and optionally other constituent gases.

As shown in FIG. 1a, the first electrode 104 and the second electrode 105 of the PP apparatus 100 are arranged apart from each other and generate an electric field in the reaction zone 103 to generate nanoparticles and / or aggregates thereof and the like. The plasmapolymer nanoparticle material of is configured to form from at least one monomer in the form of a gas. The distance between the first electrode 104 and the second electrode 105 can be, for example, about 5 cm to about 60 cm. In some embodiments, the device 100 is a linear motion device capable of moving the first and / or second electrodes 104, 105 to change the distance between the first and second electrodes 104, 105. Can be prepared.

The first electrode 104 may have, for example, a radius of about 4 cm to about 19.9 cm and a depth of about 0.5 cm to about 5 cm. The first electrode 104 and / or the second electrode 105 can be made of, for example, stainless steel (eg, 304 or 316L), aluminum, or graphite.

Power can be applied to the first electrode 104, the second electrode 105, or both electrodes. In some embodiments, the first electrode 104 is connected to a power source and the second electrode 105 is electrically isolated to obtain a stray potential determined by the charging of the electrode in the discharge of the reaction zone 103. Or may be connected to a pulsed high voltage power supply.

The power applied to the first electrode 104 should be sufficient to generate and maintain a plasma discharge in the reaction zone 103. It should be sufficient to fragment, dissociate, or ionize a mixture of gases such as hydrocarbon gas, reactive non-polymerizable gas, and additional gases such as nitrogen, the fragment of which is the resulting polymeric material. Can be incorporated into. It should be sufficient to generate radical species in the plasma discharge of reaction zone 103 due to gas dissociation and fragmentation. It should be sufficient to maintain the plasma discharge in the reaction zone 103 during the formation of the nanoparticle material in the reaction zone 103.

In some embodiments, the power supply connected to the first electrode 104 supplies the first electrode 104 with radio frequency (rf), or DC, or pulsed radio frequency, or pulsed DC power. Plasma can be generated and maintained inside the reaction zone 103. For example, during plasma generation, the rf frequency is about 1 to about 200 MHz and can be supplied to the first electrode 104 with a power of about 5 to about 500 or about 5 to 3000 W. As another example, the pulse bias voltage can be supplied to the first electrode 104 with a frequency of about 1 Hz to about 50 kHz and a pulse duration of about 1 to about 150 microseconds. The ratio between the pulse off time and the pulse on time can be from about 10 (ie, 10: 1) to about 20. The bias voltage can be from about −1000V to about 1000V. In some embodiments, the bias voltage is non-zero. Therefore, it can be either positive or negative, and in either case the absolute value can be 10 to 1000.

During plasma generation, the pressure inside the reaction zone 103 or vacuum chamber 101 is about 7.5 mTorr to about 115 mTorr (absolute pressure is about 1 to about 1500 Pa) or about 7.5 mTorr to about 760 mTorr (absolute pressure is about 1 to about 101325 Pa). ) Can be between. To achieve the desired pressure, the vacuum chamber 101 can initially be evacuated below this pressure, eg, less than about 10 mPa. The gas or its individual constituent gases are then bleeded into the vacuum chamber 101 and the reaction zone 103 through the gas inlet 102 at a sufficient rate coordinated with the pump speed to give the desired pressure and desired pressure in the reaction zone 103. The desired pressure is achieved by making it possible to achieve the monomer residence time of. The residence time, pressure, gas flow rate, and power of the gas molecules associated with the plasma in the reaction zone 103 determine the degree of fragmentation of the plasma monomers and other gas molecules. It will be appreciated that the required flow rate depends on the size of the vacuum chamber 101. However, by monitoring the pressure inside the vacuum chamber 101 (eg, by a pressure gauge tied to the internal space of the vacuum chamber 101), the flow rate (s) and pump speed can be adjusted to achieve the desired pressure and gas residence time. Can be achieved. The flow rate of at least one gas (or the sum of the flow rates of all gases) can be from about 0.1 to about 4000 sccm (standard cubic centimeters / minute). The flow rates of the carrier and the reactive non-polymerizable gas (s) can then be adjusted to achieve the desired pressure inside the vacuum chamber 101 and the residence time inside the reaction zone 103.

It will be appreciated that any of the flow rate, pressure, and power can be varied according to the particularly desired properties of the plasma polymer nanoparticle material formed in the reaction zone 103. Thus, any of the numbers or ranges exemplified herein for each of flow rate, pressure, and power can be used together in any combination. For example, in one embodiment, a flow rate of about 0.5 to about 10 sccm, a pressure of about 20 Pa, and a power of about 50 W to about 100 W can be used. All other possible combinations are envisioned herein.

In one embodiment of the present disclosure, the first electrode 104 is connected to a radio frequency (rf) power source and the second electrode 105 floats and has a floating potential determined by its spontaneous charging in the discharge of the reaction zone 103. Can be achieved.

The plasma polymer nanoparticle material formed by the reactive plasma as described above can be collected using a plurality of collectors. Each collector 1061 of the plurality of collectors 106 may be fixed to each other or may be independently movable. Each collector can have a three-dimensional shape and can demarcate recesses or receiving portions. The plurality of collectors 106 may be removable from the reaction zone 103 and the vacuum chamber 101, for example by being included in or placed in a removable plate. Referring to FIG. 1a, in this embodiment, the plurality of collectors 106 are arranged between the first electrode 104 and the second electrode 105 to collect the plasma polymer nanoparticle material formed in the reaction zone 103. It is configured as follows.

The collectors 1061 of the plurality of collectors 106 are fixed to each other, or the plurality of collectors 106 are circular, square, oval, rectangular, triangular, pentagonal, hexagonal, etc., or substantially circular. It may have a structure having an outer shape such as a substantially square, a substantially elliptical shape, a substantially rectangular shape, a substantially triangular shape, a substantially pentagonal shape, a substantially hexagonal shape, or the like. The structure can be n-sided. Examples include rectangles, squares (n = 4), parallelograms (Σ2ni = 4, i = i1, 2), pentagons (n = 5), hexagons (n = 5) and the like. The range of equilateral length n can be from about 1 cm to about 50 cm. For example, the plurality of collectors 106 may be on a rectangular tissue culture plate measuring 127.89 x 85.60 mm (ie, total area 108 cm ² , sides n ₁ = 127.89 mm, and n _{2 = 85.60 mm).} Can be included.

In one embodiment, the plurality of collectors 106 include a plurality of vials 1061, as shown, for example, in FIG. 1a. Alternatively, or in addition, as shown in FIG. 2a showing, for example, a plasma polymerization (PP) apparatus 200 according to another embodiment of the present disclosure performing functions similar to those described above with reference to FIG. 1a. Collector 206 may include a plurality of wells 2061. For example, the plurality of collectors 206 may include a plurality of wells 2061 formed on the collector (well) plate 206, which collector plate 206 may be removable from the reaction zone 203.

The shape and size of each individual collector 1061, 2061 is important as it controls particle agglutination, whether provided by a vial, well, or otherwise. The size and shape of each collector (or at least its recesses or receiving portions) can be selected based on the desired size and yield of the nanoparticle material. In some embodiments of the present disclosure, collectors, such as vials and / or wells (or at least recesses or receiving portions thereof), can each have a depth of about 2 to about 20 mm. In some cases, the vials and / or wells may each be deeper than 20 mm. As an example, if the vials or wells are substantially circular, the radius of one or more vials or wells can be from about 1 mm to about 50 mm. The ratio of height to radius of each vial or well can be adjusted according to the desired size and yield of the nanoparticle material. In one example, the ratio of height to radius of the well is about 5: 1 to 0.1: 1.

In the device shown in FIG. 2 having a plurality of circular wells 2061, each well 2061 may have a height of about 8.00 mm to about 17.40 mm. Each well 2061 may have a radius of about 3.43 mm to about 8.13 mm. For example, the well can have a height = 17.40 and a radius = 8.13 mm, or a height = 10.67 and a radius = 3.43 mm, or a height = 8.00 and a radius = 7.00 mm.

The plurality of collectors 106, 206 may be hermetically sealable. Thus, the vials or wells 1061 and 2061 may be individually or collectively sealable. Since each vial or well is effectively sterilized when exposed to plasma, collecting nanoparticle material directly in each vial or well provides a convenient way to collect and sterilize the vial or well in a single step. Can be done. The collector may be made of a non-conductive material or may be made of a conductive material. The collector may be made of a material that can withstand the plasma. Collectors include, for example, low degassing polymers such as stainless steel, aluminum, copper, polystyrene, high density polystyrene, acrylonitrile butadiene styrene, polycarbonate, polyethylene (including high density polyethylene, low density polyethylene), polypropylene, polyamide, polyacetylene, polypropylene. , Glass (silica-silicon dioxide), quartz, and / or silicon (semi-conductive crystalline wafer) can be formed.

The nanoparticles formed by the devices 100, 200 undergo a thermophoretic force due to the temperature gradient inside the reaction zones 103, 203. The thermophoretic force results from the efficiency of higher momentum between the plasma / gas seed and the particles in the hot region. We have determined that the temperature gradient can be advantageously used to push the particles of reaction zone 103 from the hotter region to the cooler region. In particular, the temperature gradient can be adjusted to control the movement of particles towards and into the plurality of collectors 106, 206. In this embodiment, a suitable temperature gradient is generated by cooling a plurality of collectors 106, 206. A large temperature gradient can be obtained by cooling the plurality of collectors 106, 206 to a temperature significantly lower than the temperature of the plasma / gas in the reaction zones 103, 203. For sufficiently large temperature gradients, the thermophoretic force may outweigh the ion and gas attraction of the particles. Ultimately, this can provide higher nanoparticle yields at multiple collectors 106, 206, expanding the range of collectable particle sizes. For example, with a wider range of particle sizes, the net attraction force that pushes the particle towards multiple collectors (ie, the sum of gas attraction, ion attraction, and thermophoretic force) is enabled and confined. It can exceed any electrostatic force that exists.

Referring to FIG. 1, cooling can be achieved, for example, by thermally coupling the plurality of collectors 106 to the cooling device 107, eg, one of the plurality of collectors or another structure comprising the plurality of collectors. The above surface can be achieved by directly contacting the cooling surface of the cooling device 107 or by contacting and arranging the surface via a heat transfer medium. The cooling device 107 may include a single cooling device or array and / or a cascade of cooling devices, such as a thermoelectric semiconductor device, such as one or more Pelche semiconductor devices. The cooling device 107 can be arranged between the first electrode 104 and the second electrode 105. The cooling device 107 can be arranged between the plurality of collectors 106 and the second electrode 107. The cooling device 107 may be able to cool at least a portion of each collector 1061 below the temperature of the plasma during the synthesis of the nanoparticle material in the reaction zone 103. Cooling by the cooling device 107 can cool the walls of each collector 1061.

In one embodiment, the thermal coupling between the plurality of collectors 106 and the cooling device 107 is via a vacuum compatible high thermal conductivity thermal paste or pad located between the plurality of collectors 106 and the cooling device 107. Can be achieved. The area of the cooling surface of the cooling device 107 can be the same as the area of the surface of the plurality of collectors 106 coupled to the cooling device 107.

Also, if multiple cooling devices are provided, for example in an array or cascade, thermal coupling between adjacent cooling devices can be provided to ensure efficient heat transfer between them. Coupling between the cooler arrays can also be achieved via a vacuum compatible high thermal conductivity (eg, 3W / mK, 6W / mK, 12W / mK or higher) thermal paste or pad.

As shown, the cooling device 107 may include at least one Pelche element. In some cases, the surface area of the largest commercially available thermoelectric element may be smaller than the surface area of the plurality of collectors to be cooled (eg, 100 x 100 mm). In this situation, an array of Pelche elements can be used to achieve uniform cooling throughout the collector.

The thermoelectric cooling can operate, for example, in a voltage range between about 2V and 30V, and can draw a total current, for example, between about 2A and 40A. The maximum temperature difference between the "warming side" and the "cooling side" of the Pelche element can be in the range of 1 ° C to 80 ° C. In the case of the Pelche elements stacked in a cascade, the voltage applied to the lower element (the one closest to the plurality of collectors) may be higher than the upper element (the one closest to the plurality of collectors). In one embodiment in which the two elements are stacked in a cascade, the voltage applied to the lower element can be 12V and the voltage applied to the upper element can be 5V. In another embodiment, the voltage applied to the lower element 107a is as shown in FIG. 1b, where the three elements are stacked in a cascade and show a portion of the device 100 of FIG. 1a with respect to the modified cooling device. It can be 12V, the voltage applied to the central element 107b can be 5V, and the voltage applied to the upper element 107c can be 3.3V.

Referring to FIGS. 2a and 2b, in one embodiment, the cooling device 207 may be an array of thermoelectric semiconductor devices such as a Peltier device thermally coupled to the back surface of the collector plate 206, where the collector plate is a plurality of wells 2061. To prepare for. The cooling side 2071 of the cooling device 207 adjacent to and facing the collector plate 206 cools the collector plate 206. The temperature of the collector plate 206 can be stabilized and kept constant by providing efficient heat dissipation to the warming side 2072 on the opposite side of the cooling device 207. Efficient dissipation of heat generated by the heating side 2072 of the cooling device 201 can be achieved using the heat exchanger 201 which can be thermally coupled to the cooling device 207. The heat exchanger 201 may include, for example, a passive component such as a heat sink, as shown in FIGS. 2a and 2b. The heat sink may include a large surface area, for example by including a plurality of fins 2011.

Additional or alternative, the heat exchanger is made of a metal pipe (eg, copper or stainless steel) that contacts the heat transfer fluid (eg, water, liquid nitrogen, helium) with the warming side 2072 of the cooling device 207. It may contain active components such as a closed cooling loop that constantly flows through.

Additional or alternative, the heat sink may include active components for enhancing heat dissipation, such as fans and / or copper heat pipes. In one embodiment, by way of example, the extension portion of the heat sink is configured to extend outside the vacuum chamber in which the device 200 is located. The fan can be coupled to a portion of the heat sink that extends outside the vacuum chamber.

As shown in FIG. 2, in some embodiments, the second electrode 205 is at least partially accepted by one or more of the following cooling devices 207, collector plate 206, and heat exchanger 201: The recess 2051 is provided. For example, according to the embodiment shown in FIG. 2a, at least the cooling device 207 can be completely accommodated in the recess 2051. The recess may be open on one side to accommodate the collector plate 206 at least partially.

As shown in FIG. 2a, the PP apparatus 200 according to the present disclosure may further include confinement means such as confinement grid 202. The confinement grid 202 can extend between the first electrode 204 and the second electrode 205. The confinement grid 202 can be grounded or capable of acquiring a potential determined by charging of the confinement grid upon exposure to plasma. In this regard, or otherwise, the confinement grid 202 can be considered to include a third electrode. The confinement grid 202 can substantially confine the plasma between the first electrode 204 and the plurality of collectors 206 by confining the electric field. The confinement grid 202 can inhibit the lateral expansion of the plasma and its diffusion into the walls of the surrounding vacuum chamber. In some embodiments, the confinement grid can also confine and / or define the reaction zone 203. Since the nanoparticle material formed in the plasma is confined by the positive plasma potential of the reaction zone 203, the particle loss is confined within the boundaries defined by the confinement grid 203 in the reaction zone 203 (and ultimately the plasma and nanoparticles). It can be significantly suppressed by confining the material).

The confinement grid 203 may include, for example, a mesh with a plurality of openings 2021, as shown in FIG. 2a. Each opening of the mesh can have a maximum dimension, for example, between about 50 μm and 5 mm. By way of example only, the mesh opening 2021 of the confinement grid 203 can be substantially circular, square, oval, rectangular, triangular, pentagonal, hexagonal. When combined, the openings can be provided with, for example, a circular, rectangular, honeycomb, or triangular mesh confinement structure. Each opening 2021 may be uniform in shape and / or size. Alternatively, it may have openings of different shapes and / or sizes.

The confinement grid 203 may be made of a conductive or non-conductive material. The confinement grid 203 may be made of a material that can withstand plasma. The confinement grid 203 may be made of, for example, stainless steel, aluminum, and / or copper. The confinement grid 203 may have an overall structure that is tubular or partially tubular. The cross section of the confinement grid 203, eg, its widthwise cross section across a plane perpendicular to the axis extending between the first and second electrodes 204, 205, is substantially circular, square, oval, rectangular, triangular, It can be pentagonal or hexagonal. For example, as is apparent from FIGS. 2a and 2b, the cross section is circular and therefore the confinement grid 203 has a substantially cylindrical structure.

The confinement grid 203 may have a maximum width of about 5 cm to about 20 cm. The confinement grid 203 may have a maximum width substantially equal to or greater than the maximum width of the first and / or second electrodes 204, 205.

The length of the confinement grid 203 extending between the first and second electrodes 204, 205 can be, for example, about 3 cm to about 30 cm. The confinement grid 203 may have a length substantially equal to or longer than the distance between the first and second electrodes 204, 205.

The configurations described herein may allow PP devices 100, 200 to enhance the collection of plasma polymer nanoparticle materials formed with reactive plasmas. As an example, the process yield can be increased by increasing the thermophoretic force as the plurality of collectors 106, 206 are cooled by the cooling devices 107, 207, with the plurality of collectors 106, 206 in the reaction zones 103, 203. More particles will pass through the net pulling force towards them. The improvement in yield can be further achieved by confining the plasma boundaries of the reaction zones 103, 203 using the confinement grid 202.

Although not shown in FIGS. 1 and 2, the PP devices 100, 200 according to the present disclosure may include a controller 310 for controlling the cooling applied by the cooling devices 107, 207. By controlling the cooling, the controller can then control the yield and / or properties of the particles collected by the plurality of collectors 106, 206.

In one example, as shown in FIG. 3, the controller 301 adjusts the power (eg, voltage) supplied to the cooling devices 107, 207 by the power supply 302 to provide cooling applied by the cooling devices 107, 207. The degree can be controlled. The controller 301 is based on the input from the user interface 303 and / or based on the input from the particle sensor 304 and / or based on the input from the temperature measuring device 305 and / or from the plasma diagnostic device 306. The power can be adjusted based on the input.

The user interface 303 may include one or more buttons, dials, keyboards, touch sensitive screens, or the like, through which the user may select the desired particle properties.

The particle sensor 304 may include, for example, a scanner that scans particles located in plasma, reaction zones 103, 203, and / or a plurality of collectors 106, 206. The particle sensor 304 may include, for example, a camera that detects the intensity and spatial distribution of light emitted from a laser source scattered on a nanoparticle material. The temperature measuring device 305 may include, for example, a plurality of collectors 106, 206 or thermocouples in contact with individual wells / vials 1061, 2061. The plasma diagnostic device 306 may include an array of Langmuir probes for measuring relevant plasma output parameters such as electron temperature and density at different locations in the reaction zone, eg, near multiple collectors 106, 206. Additional or alternative, the plasma diagnostic device 306 is an enhanced charge coupling device image sensor and an optical spectroscope coupled to an optical fiber to collect the radiation emitted by the plasma at different locations within the reaction zones 103, 203. (Or monochromator) may be included. The discharge emission intensity is, for example, PCT Publication No. WO2018 / 112543 on page 72, lines 19 to 28, page 79, line 3 to page 80, line 27, and FIGS. 5, 6, and 11 to 15. , 17 and 18, which can vibrate during the formation, growth, and removal of the nanoparticle material in the reaction chamber. The vibration period and relative intensity are related to the chemistry, size, and yield of the nanoparticles. Thus, the particle sensor 304, the temperature measuring device 305, and / or the plasma diagnostic device 306 can be used, for example, to calculate the current particle properties of the particles produced using the device, and the current particle properties. Depending on the difference between Can be adjusted. In this regard, the device adjusts plasma input parameters (such as combined power, gas flow and / or discharge pressure) based on sensed particle characteristics, plasma diagnostics, and / or temperature measurements of multiple collectors. It may include a feedback loop that adjusts the particle properties and / or adjusts the yield and thermostatic power of the particles using cooling control.

Particle properties can individually include the average or average size of nanoparticles or aggregates of nanoparticles, the number of nanoparticles or aggregates of nanoparticles, or the chemistry of nanoparticles or aggregates of nanoparticles.

The controller 301 may include a processor. The processors disclosed herein may include several control or processing modules for controlling one or more functions of the device and method, as well as data such as scan data, desired particle properties or others. May include one or more storage elements for storing. Modules and storage elements can be implemented using one or more processing devices and one or more data storage devices, and these modules and / or storage devices are in one place or more than one. It is distributed across locations and can be interconnected by one or more communication links. The processing equipment used shall be placed on other types of processing equipment, including desktop computers, laptop computers, tablets, smartphones, personal digital assistants, and equipment specially manufactured to perform the functions according to the present disclosure. Can be done.

Further, the processing module can be implemented by a computer program or program code including program instructions. Computer program instructions can include source code, object code, machine code, or any other stored data that can be operated to cause the processor to perform the steps described. Computer programs may be written in any form of programming language, including compiled or interpreted languages, including stand-alone programs or modules, components, subroutines, or other units suitable for use in a computing environment. It may be developed in this format. The data storage device (s) may include a suitable computer-readable medium such as volatile (eg, RAM) and / or non-volatile (eg, ROM, disk) memory, or the like.

Example 1-To illustrate the collection of plasmapolymer nanoparticles or nanoparticle materials (PPNs) in capacitively coupled radio frequency dust plasmas of _{C 2} H ₂ / N ₂ / Ar where the shape of the collector controls particle agglomeration. , Multiple wells included in the removable well plate were used (according to those described in PCT Publication No. WO 2018/112543). A well plate was placed above the floating substrate holder (second lower electrode) to confine the PPN within the boundaries of each well (FIG. 4a). For comparison, experiments were also performed on wellless stainless steel (SS) sheets, as shown in FIG. 4b, with conventional flat (two-dimensional) substrate shapes widely used in plasma polymer coating deposition. It was made possible to directly compare with the sample. As shown in FIG. 4b, the conventional two-dimensional shape (without wells) usually produces a plasma polymer material in the form of a thin film coating (see, eg, Santos et al. 2016, ACS Applied Materials & Surfaces). .. The use of a 3D well plate collector has been shown to achieve a significant increase in PPN yield compared to conventional 2D collectors, and the well aspect ratio of the well plate collector is also PPN aggregation, size, and It has been shown to regulate the polydispersity index (see PCT publication number WO2018 / 112543). The collection efficiency of different well plates is initially illustrated using 8.5 cm x 12.7 cm polystyrene tissue culture plates, where the plates are 4 rows (A to D) x 6 columns (1 to 6) wells. It contains 24 wells dispersed in a matrix. Each well had a depth of 1.7 cm and a surface area of 2 cm ² . Exposure of the well plate to dust plasma for 7 minutes (corresponding to 5 complete PPN growth cycles) resulted in a significant change in the appearance of the plate due to the deposition of powdery brown material. High-resolution secondary electron images of the nanoparticles as they were synthesized were taken. For the purpose of imaging samples using a scanning electron microscope (SEM), plasma is performed in a single growth cycle (ie, 80 seconds) to avoid superposition of multiple generation nanoparticles. Was set to. The resulting SS surface was covered with a large number of spherical nanoparticles characterized by topography of the cauliflower-like surface. The nanoparticles were evenly distributed throughout the sheet, covering 29% of the sheet surface, and mostly placed in aggregates formed by aggregates of particles from 3 to 20. Interestingly, no coating formation was observed on the surface placed inside the plate collector, suggesting that no surface polymerization occurs at the bottom of the wells. Therefore, this collection method gave a sample of pure nanoparticles without a coating. In contrast, plasma polymer coatings are typically the same on SS sheets placed in substrate holders in a flat configuration (ie, without a plate collector), usually (see, eg, Santos et al. 2016, ACS Applied Materials & Surfaces). Obtained under discharge parameters. Diffusion of the active species from the plasma and subsequent polymerization of the surface resulted in a uniform golden coating on the substrate. The morphology of the coating suggested that surface plasma polymerization occurred locally in islands and then fused to formally cover the underlying substrate. The deposition of nanoparticles on a flat substrate is virtually negligible and covers less than 1% of the surface.

The forces that are understood to act on the PPNs on the outside and inside of the collector well during synthesis are shown in FIG. For PPNs with a flat two-dimensional collector (left side of FIG. 5), the PPN floats in a vertical equilibrium position near the plasma sheath on a flat substrate. The net ion attraction (due to the horizontal component) by the ion flux towards the walls of the chamber pulls the particles out of the substrate region, resulting in the deposition of a low particle count coating. In contrast, in the case of a PPN in which a well-type 3D substrate, such as a well plate (see the right side of FIG. 5), is present, the expansion of the plasma draws the PPN into the well. The net pulling force (due to the vertical and downward components) pulls the trapped particles towards the bottom of the well. No coating deposits on the bottom of the well.

FIG. 6 shows how the ratio of height (h) to radius (r) of each vial or well affects the distribution of plasma within each well that regulates PPN aggregation. Due to the higher wells (FIG. 6a), the plasma cannot extend the full length of the wells and the PPN particles are continuously drawn towards the bottom of the wells outside the plasma region, resulting in reduced surface charge. And aggregate. As the plasma expands through the height of the wells, the aggregation of PPN particles is significantly suppressed when the length of the wells is reduced (ie, the wells are short) (FIG. 6b). Therefore, the dimensions of the collector can be varied to produce nanoparticles and aggregates of preferred size.

Cooling device for increasing the yield of nanoparticles using the multi-collector, plate of Example 2-3D Collection of plasma polymer nanoparticles material or nanoparticles (PPN) is generally performed in FIGS. 1a, 1b, 2a and FIGS. It was carried out in the same manner as in Example 1 except that an active cooling device was added according to the embodiment described herein with reference to 2b.

_{The PPN in the plasma is thermophores, that is, the thermodynamic force (Ft} ) that the nanoparticles in the gas result from better momentum efficiency between the plasma / gas seeds and the particles in the hot region. May show phenomena that show different responses.

The well plate is thermally coupled to different configurations of the Pelce elements, including a single Pelce element and two Pelce elements mounted in a cascade configuration (stacked together), with different heat exchanger configurations. Thereby, different temperature gradients were achieved.

FIG. 7 shows various temperature profiles measured on the surface of a plate using both a single thermoelectric cooling and a cascade-mounted dual thermoelectric cooling. The heat exchanger, which was heat-coupled to the Pelche element (s), was equipped with a copper heat pipe to help dissipate the heat. The voltage applied to the Pelche element (single configuration) was 12V, and the maximum current was 10A. The voltage applied to the upper Pelche element (heat-coupled to the well collector) in the double cascade configuration is 5V, the total current is 4A, and the lower Pelce element (heat-coupled to the heat exchanger) in the double cascade configuration. ) Was 12V and the maximum current was 10A.

Using a single configuration, the temperature measured at the bottom of the well dropped at an average rate of -0.57 ° C / sec, about 60 seconds after activating the Pelche element, before reaching a minimum of -11 ° C. Next, the heat generated by the "warming side" of the Pelche element exceeded the heat dissipation capacity of the heat exchanger, so that the temperature rose at a constant rate of 0.1 ° C./sec. Using the double cascade configuration, the minimum temperature was also achieved at about 60 seconds, but was significantly lower at -27.4 ° C and the average temperature drop was -0.84 ° C / sec. The temperature rise was the same as 0.1 ° C./sec in the single element configuration.

Heat exchange utilizing a custom vacuum feedthrough by enhancing the heat dissipation on the warm side of the Pelche element to stabilize the temperature of the well collector and verify that it can be kept constant at low temperatures. Most of the vessel was placed so as to extend outside the vacuum chamber. The fan was coupled to the heat exchanger to increase the heat dissipation capacity. FIG. 8 also shows the temperature profile of the configuration of single and double Pelche elements in which a fan was used to dissipate the heat stored by the heat exchanger. The minimum temperature of the single element configuration reached after 60 seconds and remained constant at -14.4 ° C. during the assay. The temperature measured at the bottom of the wells of the dual Pelce device configuration was significantly lower, reaching -30 ° C in 60 seconds and further dropping from 180 seconds to -32 ° C during the assay.

Therefore, using a fan coupled to a heat sink outside the vacuum chamber provides a cost effective and simple solution for enhancing heat dissipation. This allows a temperature gradient (up to 1840 K / m) between the plasma bulk and the bottom of the PP device 100 to be maintained throughout the process and ultimately increases the yield of nanoparticles in each synthesis run.

It will be appreciated by those skilled in the art that many modifications and / or modifications can be made to the above embodiments without departing from the broad overall scope of the present disclosure. Therefore, this embodiment should be regarded as exemplary in all respects and not limiting.

Claims (49)

It is a plasma polymerization device,
Reaction zone,
At least one gas inlet for supplying at least one monomer in the form of a gas to the reaction zone,
First and second electrodes, spaced apart and configured to generate an electric field in the reaction zone to form a plasmapolymer nanoparticle material from the at least one monomer.
A plurality of collectors configured to collect the plasma polymer nanoparticle material formed in the reaction zone, the plurality of collectors arranged adjacent to the second electrode, and the second collector. The plasma polymerization apparatus comprising a cooling apparatus disposed adjacent to an electrode and configured to cool the plurality of collectors. The device according to claim 1, wherein the cooling device is arranged between the plurality of collectors and the second electrode. The device according to claim 1 or 2, wherein the cooling device includes one or more thermoelectric semiconductor devices. The device according to claim 3, wherein the cooling device includes one or more Peltier devices. The device according to any one of claims 1 to 4, wherein the cooling device is coupled to the back surface of the plurality of collectors. The apparatus according to any one of claims 1 to 5, wherein the plurality of collectors include a plurality of vials or wells. 6. The device of claim 6, comprising at least 12, 24, 48 or 96 vials or wells. The device of claim 6 or 7, wherein the plurality of collectors are provided in the well plate. The apparatus according to any one of claims 1 to 8, wherein the plurality of collectors are removable from the reaction zone. The device according to any one of claims 1 to 9, wherein the cooling device is coupled to a heat exchanger. 10. The apparatus of claim 10, wherein the heat exchanger comprises a heat sink comprising a plurality of fins. 10. The device of claim 10 or 11, wherein the heat exchanger comprises a cooling loop through which a heat transfer fluid flows. The device according to claim 10, 11 or 12, wherein the heat exchanger includes a plurality of heat exchange pipes. The device according to any one of claims 10 to 13, wherein at least a part of the heat exchanger protrudes from the device for supplying the outside of the vacuum chamber. The device according to any one of claims 10 to 14, comprising a fan configured to cool the heat exchanger. 14. The device of claim 14, comprising a fan configured to cool the overhanging portion of the heat exchanger. The apparatus according to any one of claims 1 to 16, comprising a confinement grid for confining the electric field in the reaction zone. 17. The device of claim 17, wherein the confinement grid extends between the first electrode and the second electrode. 18. The apparatus of claim 18, wherein the confinement grid comprises a mesh having a plurality of openings. 19. The apparatus of claim 19, wherein each of the openings has a maximum dimension between about 50 μm and 5 mm. 19. The apparatus of claim 19 or 20, wherein each of the openings is substantially circular, square, oval, rectangular, triangular, pentagonal, or hexagonal. The device according to any one of claims 17 to 21, wherein the confinement grid has a tubular or partially tubular structure. 22. The apparatus of claim 22, wherein the structure has a substantially circular, square, oval, rectangular, triangular, pentagonal or hexagonal cross section. The device according to any one of claims 17 to 23, wherein the confinement grid has a maximum width substantially equal to or larger than the maximum width of the first and / or second electrodes. The apparatus according to any one of claims 1 to 24, further comprising a controller for controlling the formation of the plasma polymer nanoparticle material in the reaction zone. 25. The device of claim 25, wherein the controller controls the cooling applied by the cooling device. 25. The device of claim 25 or 26, wherein the controller controls plasma input parameters. Claimed that the plasma input parameter comprises one or more of power to the first or second electrode, flow rate of gas supplied to the reaction zone, and / or pressure of gas in the reaction zone. 27. The controller controls the cooling applied by the cooling device by adjusting the power supplied by the power source to the cooling device and / or the period during which the power is supplied to the cooling device by the power source. The device according to any one of claims 25 to 28. The device according to any one of claims 25 to 29, which includes a user interface and is controlled by the controller based on an input from the user interface. The device according to any one of claims 25 to 30, which includes a particle sensor and is controlled by the controller based on an input from the particle sensor. 31. The apparatus of claim 31, wherein the particle sensor measures at least one property of the nanoparticle material in the reaction zone. 32. The apparatus of claim 32, wherein the at least one property is one or more of the size of the nanoparticles or agglomerates of nanoparticles, or the number of nanoparticles or agglomerates of nanoparticles. The device according to any one of claims 25 to 33, which includes a temperature measuring device and is controlled by the controller based on an input from the temperature measuring device. The device according to any one of claims 25 to 34, which includes a plasma diagnostic device and is controlled by the controller based on an input from the plasma diagnostic device. Claims 1-35, wherein the second electrode comprises a recess in which (a) the plurality of collectors are at least partially accepted and / or (b) the cooling device is at least partially accepted. The device according to any one of the above. The second electrode is according to any one of claims 10 to 16, or any one of claims 10 to 16, wherein the heat exchanger includes at least a partially accepted recess. The device according to claim 36 in the case of subordination. The device according to any one of claims 1 to 37, wherein the reaction zone, a first electrode, a second electrode, a plurality of collectors, and a cooling device are arranged in a reaction chamber. 38. The apparatus of claim 38, wherein the confinement grid is located in the reaction chamber and is dependent on claim 17. 38. The device of claim 38 or 39, wherein the reaction chamber is a vacuum chamber. It is a plasma polymerization device,
Reaction zone,
At least one gas inlet for supplying at least one monomer in the form of a gas to the reaction zone,
First and second electrodes, spaced apart and configured to generate an electric field in the reaction zone to form a plasmapolymer nanoparticle material from the at least one monomer.
A plurality of collectors configured to collect the plasma polymer nanoparticle material formed in the reaction zone, the plurality of collectors arranged adjacent to the second electrode, and the first collector. The plasma polymerization apparatus comprising a confinement grid extending between an electrode and the second electrode. 41. The apparatus of claim 41, wherein the confinement grid comprises a mesh having a plurality of openings. 42. The apparatus of claim 42, wherein each of the openings has a maximum dimension between about 50 μm and 5 mm. 42 or 43. The apparatus of claim 42 or 43, wherein each of the openings is substantially circular, square, oval, rectangular, triangular, pentagonal, or hexagonal. The device according to any one of claims 41 to 44, wherein the confinement grid has a tubular or partially tubular structure. 45. The apparatus of claim 45, wherein the structure has a substantially circular, square, oval, rectangular, triangular, pentagonal or hexagonal cross section. The apparatus according to any one of claims 41 to 46, wherein the confinement grid has a maximum width substantially equal to or larger than the maximum width of the first and / or second electrodes. A method of collecting plasma polymer nanoparticle materials
Supplying the reaction zone with at least one monomer in the form of a gas,
Creating an electric field in the reaction zone between the first electrode and the second electrode spaced apart from the first electrode to form the plasmapolymer nanoparticle material from the at least one monomer. ,
The plasma polymer nanoparticle material formed in the reaction zone is collected in a plurality of collectors adjacent to the second electrode, and a cooling device arranged adjacent to the second electrode is used. The method comprising cooling multiple collectors. A method of collecting plasma polymer nanoparticle materials
Supplying the reaction zone with at least one monomer in the form of a gas,
Creating an electric field in the reaction zone between the first electrode and the second electrode spaced apart from the first electrode to form the plasmapolymer nanoparticle material from the at least one monomer. ,
The plasma was confined using a confinement grid extending between the first electrode and the second electrode, and was formed in the reaction zone at a plurality of collectors adjacent to the second electrode. The method comprising collecting a plasma polymer nanoparticle material.

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